Cocaine addiction is a problem in the U.S. and around the world. Initial research into the abuse of cocaine revealed its addictive effects on the human body. Cocaine's addictive effects are thought to be related to its binding to several neurotransrnitter transporters, especially the dopamine transporter (DAT) [unreadable] [unreadable] Cocaine is a doparnine reuptake inhibitor which causes less dopamine to be taken up by the DAT. The GBR series of dialkyl piperazines have been identified as selective dopamine uptake inhibitors that could be used to treat cocaine addiction. These compounds have been explored in the laboratory using traditional structure-activity relationship techniques, but pharmacophore development using molecular modeling methods have not been performed on them.The proposed research is a comprehensive molecular modeling study of 300 GBR analogs. [unreadable] [unreadable] The purpose of the study is to identify two pharmacophores: one for the DAT binding site and one for dopamine uptake at the DAT. The pharmacophores will be developed using a Comparative Molecular Field Analysis (CoMFA) study performed in vacuum, and the results refined by repeating the study in solvent. The Partial Least Squares method will be used to model the CoMFA results versus the binding and reuptake data. A bioactive conformer will be selected based on the most predictive model, then used as the basis for the pharmacophores